Reversed mutation rates of KRAS and EGFR genes in adenocarcinoma of the lung in Taiwan and their implications.
BACKGROUND
In western countries, the Kirsten ras oncogene homolog gene (KRAS) mutation rate is high in patients with nonsmall cell lung cancer (NSCLC), especially in those with adenocarcinoma (30%-50%), but the epidermal growth factor receptor gene (EGFR) mutation rate is very low (3%-8%). In addition, KRAS mutations reportedly were associated with EGFR tyrosine kinase inhibitor (EGFR-TKI) resistance. In Taiwan, high EGFR mutation rates associated with high EGFR-TKI response rates in patients with NSCLC have been reported; however, KRAS mutation data are limited and have not been correlated with TKI response.


METHODS
KRAS mutation analysis was performed on 237 NSCLC specimens, and the results were correlated with clinicopathologic features. All but 2 tumors also underwent EGFR mutation analysis.


RESULTS
KRAS mutations were identified in only 9 of 237 patients (3.80%). Five patients were women who were nonsmokers, and 4 patients were men who were ever-smokers. The mutation rate was 5.03% in patients with adenocarcinoma (8 of 159 patients) and 1.56% in patients with squamous cell carcinoma (1 of 64 patients). Four mutations were G12V, 3 mutations were G12D, 1 mutation was L19F, and 1 was the duplication insertion mutation dupT50_M72. In contrast, EGFR mutations were detected in 96 of 235 patients (40.8%) and in 90 of 157 adenocarcinomas (57.3%). None of the KRAS mutations coexisted with EGFR mutations. KRAS mutations were not associated significantly with any clinicopathologic characteristics, including smoking status. Among the 53 patients who had received TKI monotreatment, only 1 patient had a KRAS mutation and had progressive disease.


CONCLUSIONS
The KRAS mutation rate was too low to play a significant role in TKI resistance or tumorigenesis among Taiwanese patients with NSCLC, which was the complete reverse of the results reported in western countries.
Wu
Chun-Chieh
CC
Department of Pathology, Chang Gung Memorial Hospital, Tao Yuan, Taiwan.
Hsu
Hui-Yu
HY
Liu
Hui-Ping
HP
Chang
John Wen-Cheng
JW
Chen
Ya-Ting
YT
Hsieh
Wen-Yu
WY
Hsieh
Jia-Juan
JJ
Hsieh
Meng-Shu
MS
Chen
Yi-Rong
YR
Huang
Shiu-Feng
SF
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics*; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D018773:Genes, erbB-1; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D013624:Taiwan
D047428:Protein Kinase Inhibitors